Preparation of cyclic N-tert-butylsulfonyl enamines by Rh(II)-mediated ring expansion of α-diazoesters

Article abstract of DOI:10.1055/s-2006-926449

The anion derived from ethyl diazoacetate adds to N-tert-butylsulfonyl ketimines to give β-tert-butylsulfonylamino α-diazoesters, which are further transformed into cyclic enamines by treatment with Rh ₂(OAc)₄, through 1,2-C-C bond m

Full text of DOI:10.1055/s-2006-926449

SPECIAL TOPIC
1705
Preparation of Cyclic N-tert-Butylsulfonyl Enamines by Rh(II)-Mediated Ring
Expansion of a-Diazoesters
Cyclic
N-tert
-
B
h
utylsulfony
uEnamines feng Chen, Yonghua Zhao, Jianbo Wang*
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of the Ministry of Education, College of Chemistry,
Peking University, Beijing 100871, P. R. of China
E-mail: wangjb@pku.edu.cn
Received 23 February 2006
tBuO2S
N2
Abstract: The anion derived from ethyl diazoacetate adds to N-tert-
butylsulfonyl ketimines to give b-tert-butylsulfonylamino a-diazo-
esters, which are further transformed into cyclic enamines by treat-
ment with Rh2(OAc)4, through 1,2-C–C bond migration of a Rh(II)
carbene intermediate.
tBuO2SNH
N
CO2Et
N2CHCO2Et
Base
Rh(II)
tBuO2SNH
Key words: diazo compounds, Rh(II) carbene, 1,2-C–C bond mi-
gration, ring expansion
CO2Et
Among the various catalytic transformations of a-diazo-
carbonyl compounds, the C–C bond migration is a unique
process.1 Although C–C bond migration is a less favor-
able process and in most cases is associated with other
competing reactions, it may find application in organic
synthesis in some special cases. For example, the C–C
bond migration has been nicely utilized in the ring expan-
sion of cyclic ketones via base-promoted aldol-type reac-
tion with ethyl diazoacetate (EDA), followed by
Rh2(OAc)4-catalyzed diazo decomposition (Scheme 1).2
Scheme 2 Ring expansion with cyclic N-tert-butylsulfonyl en-
amines.
expansion to afford cyclic enamines when treated with
Rh2(OAc)4.
The cyclic N-tert-butylsulfonyl ketimines 4a–g were pre-
pared from the corresponding cyclic ketones 1a–g by a
two-step procedure recently reported by Ruano and co-
workers.6 The overall yields for the two-step procedure
range from 51–62% (Table 1). The cyclic ketimines have
sufficient stability to withstand purification by column
chromatography.
N2
O
O
HO
CO2Et
CO2Et
N2CHCO2Et
THF, –78 °C
Rh(II)
We then studied the reaction of the cyclic N-tert-butylsul-
Scheme 1 Ring expansion of a cyclic ketone through Rh(II) carbene fonyl ketimines 4a–g with EDA under basic conditions.
1,2-C–C bond migration.
Previously, we reported the reaction of EDA with aromat-
ic N-tosylimines promoted by a catalytic amount of
DBU.7 However, the DBU-promoted reaction of cyclic N-
We have recently studied the similar nucleophilic addition
tert-butylsulfonyl ketimines 4a with EDA was very slow.
We then used the strong base, LDA, to generate the anion
from EDA at –78 °C.8 The EDA-derived anion added to
cyclic ketimines 4a to afford the diazo product 5a. It was
found that the addition of excess HMPA could improve
the yields and shorten the reaction time (Table 2).
of the EDA-derived anion with aromatic N-tosylimines.
Further treatment of the addition products with catalytic
Rh2(OAc)4 resulted in the predominant formation of the
1,2-C–C migration products. The products which could
result from the competing 1,2-C–H migration, a very fea-
sible process, are not observed.3,4 On the other hand, in the
Rh(II)-catalyzed reaction of b-hydroxy a-diazoesters,
only 1,2-C–H migration products are formed.5 The results
demonstrate a remarkable non-migrating group effect.
With the addition products 5a–g in hand, we then pro-
ceeded to study their Rh2(OAc)4-catalyzed diazo decom-
position reaction. For diazo compounds 5a–d, the
Rh2(OAc)4-catalyzed reaction proceeded efficiently in re-
fluxing dichloromethane to afford the corresponding ring
expansion products cyclic enamines 6a–d in excellent
yields (Scheme 3).
In this paper, we report further investigations along this
line by extending a similar reaction to cyclic imines, as
shown in Scheme 2. We demonstrate here that nucleo-
philic addition to cyclic imines works well to give the cor-
responding addition products, which can undergo ring
For the diazo compounds 5e and 5f, the corresponding
Rh2(OAc)4-catalyzed reaction was very slow. This may be
due to the steric hindrance around the diazo group, which
may impede access of the Rh(II) catalyst. The diazo de-
composition could occur at elevated temperatures by car-
SYNTHESIS 2006, No. 10, pp 1705–1710
x
x.
x
x
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0
0
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Advanced online publication: 27.04.2006
DOI: 10.1055/s-2006-926449; Art ID: C00606SS
© Georg Thieme Verlag Stuttgart · New York

1706
S. Chen et al.
SPECIAL TOPIC
tBuO2SNH
N2
Table 1 Preparation of Cyclic N-tert-Butylsulfonyl Ketimines 4a–g
t
NH
BuO2S
CO2Et
Rh2(OAc)4
CO2Et
O
R
CH2Cl2
reflux
(
)
n
(
)
n
t
(
)
n
NSOtBu
R
NSO2 Bu
Ti(OEt)4
(1.7 equiv)
1a–g
+
6a, n = 1, 95%
6b, n = 2, 93%
6c, n = 3, 90%
6d, n = 4, 91%
5a, n = 1
5b, n = 2
5c, n = 3
5d, n = 4
R
MCPBA
O
THF, reflux
CH2Cl2
r.t., 0.5 h
(
)
n
(
)
n
tBuSNH2
3a–g
4a–g
Scheme 3 Rh2(OAc)4-catalyzed reaction of 5a–d.
2
Entry
Ketone 1
Reaction Yield
time
Yield
the cases of 5f and 5g, part of the enamine products
isomerized to the corresponding ketimines 7f and 8.
1 to 3 (h) 1 to 3 (%)a 3 to 4 (%)a
In summary, we have demonstrated that EDA could add
to cyclic N-tert-butylsulfonyl ketimines with LDA as the
deprotonating agent; the addition product was treated with
a catalytic amount of Rh2(OAc)4 to effect 1,2-C–C bond
migration and afford the ring-expansion product. The
two-step procedure represents an efficient method to ac-
cess cyclic enamines.
1
2
3
4
5
6
7
1a: R = H, n = 1
1b: R = H, n = 2
1c: R = H, n = 3
1d: R = H, n = 4
6
6
6
6
9
7
6
68
69
73
77
68
89
61
87
82
85
78
85
86
83
1e: R = Me, n = 1
1f: R = Me, n = 2
1g: R = Ph, n = 2
All solvents were distilled prior to use. 1H NMR and 13C NMR spec-
tra were measured at 300 MHz and 75 MHz, respectively, on a Vari-
an Mercury 300 spectrometer or at 200 MHz and 50 MHz,
respectively, on a Varian Mercury 200 spectrometer. IR spectra
were recorded with a Nicolet AVATAR 330 FT-IR infrared spec-
trometer. Mass spectra were obtained on a VG ZAB-HS mass spec-
trometer. Elemental analyses were carried out on a Elementar Vario
EL Instrument. Column chromatography was performed on 100–
200 mesh silica gel (Qingdao, P. R. of China) employing PE–
EtOAc as eluent. PE with a bp range 30–60 °C was used; EtAOc
was distilled prior to use.
a Isolated yield after column chromatography.
rying out the reaction in refluxing 1,2-dichloroethane
(Scheme 4). Similar ring expansion gave cyclic enamines.
In the case of 5e and 5f, due to the unsymmetrical substi-
tution on the cyclic moiety, the reaction gave mixtures of
isomers. Although the structure of each isomer has not
been fully established, it is reasonable to assume the main
products are derived from the migration of the less substi-
tuted position – the less sterically hindered C–C bond. In
Caution: All diazo compounds are highly toxic or presumed to be
toxic. Diazo compounds are potentially explosive. They should be
handled with care in a well-ventilated fume hood.
Cyclic N-tert-Butyl Ketimines (4a–g)
Prepared from the corresponding cyclic ketones by a two-step pro-
cedure recently reported by Ruano and co-workers.6
Table 2 Reaction of EDA with Cyclic Ketimines 4a–g
N-Cyclopentylidine-tert-butanesulfonamide (4a)9
Rf = 0.64 (PE–EtOAc, 10:1).
N2
tBuO S
O
NH
2
CO2Et
R
LDA (1.3 equiv)
H
IR (neat): 1637, 1298, 1121 cm–1.
OEt
4a–g
+
HMPA (6.5 equiv)
THF, –78 °C
1H NMR (300 MHz, CDCl3): d = 1.47 (s, 9 H), 1.65–2.00 (m, 4 H),
2.54 (t, J = 7.5 Hz, 2 H), 2.90 (t, J = 7.5 Hz, 2 H).
N2
(
)
n
5a–g
13C NMR (75 MHz, CDCl3): d = 23.5, 23.8, 25.5, 34.8, 39.1, 58.3,
195.7.
Entry
Ketimines 4
Reaction time (h) Yield (%)a
EI-MS: m/z (%) = 203 (M+, 4), 57 (100).
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4f
8
4
62
78
50
68
45
72
62
N-Cyclohexylidine-tert-butanesulfonamide (4b)6
Rf = 0.57 (PE– EtOAc, 10:1).
7
1H NMR (200 MHz, CDCl3): d = 1.47 (s, 9 H), 1.52–1.73 (m, 2 H),
1.79–1.93 (m, 4 H), 2.39 (t, J = 6.4 Hz, 2 H), 2.95 (t, J = 6.4 Hz, 2
H).
24
24
9
13C NMR (50 MHz, CDCl3): d = 23.8, 24.9, 27.1, 27.9, 36.03, 40.3,
58.6, 193.5.
N-Cycloheptylidine-tert-butanesulfonamide (4c)
Mp 166–167 °C; Rf = 0.53 (PE–EtOAc, 10:1).
4g
8
a Isolated yield after column chromatography.
IR (neat): 1611, 1297, 1121 cm–1.
Synthesis 2006, No. 10, 1705–1710 © Thieme Stuttgart · New York

SPECIAL TOPIC
Cyclic N-tert-Butylsulfonyl Enamines
1707
N2
tBuO2SNH
CO2Et
Me
5e, n = 1
5f, n = 2
(
)
n
Rh2(OAc)4
ClCH2CH2Cl
reflux
tBuO2SNH
Me
tBuO2SNH
CO2Et
CO2Et
Me
+
(
)
n
(
)
n
6e, n = 1, 76%
6f, n = 2, 30%
6e', n = 1, 19%
6f', n = 2, 15%
tBuO2SN
Me
CO2Et
7e, n = 1, 0%
7f, n = 2, 43%
+
(
)
n
t
N2
t
HNSO2 Bu
NSO2 Bu
CO2Et
tBuO2SNH
Ph
CO2Et
Ph
CO2Et
Ph
Rh2(OAc)4
+
ClCH2CH2Cl
reflux
5g
6g, 44%
8, 43%
Scheme 4 Rh2(OAc)4-catalyzed reaction of 5e–g.
1H NMR (300 MHz, CDCl3): d = 1.46 (s, 9 H), 1.63–1.81 (m, 8 H),
2.61 (t, J = 6.2 Hz, 2 H), 3.11 (t, J = 6.0 Hz, 2 H).
EI-MS: m/z (%) = 217 (M+, 8), 57 (100).
Anal. Calcd for C10H19NO2S: C, 55.27; H, 8.81; N, 6.44. Found: C,
55.28; H, 8.82; N, 6.36.
13C NMR (75 MHz, CDCl3): d = 23.7, 24.6, 25.8, 29.5, 29.9, 37.1,
42.0, 58.5, 196.2.
N-2-Methylcyclohexylidine-tert-butanesulfonamide (4f)
Mp 41–42 °C; Rf = 0.52 (PE–EtOAc, 10:1).
EI-MS: m/z (%) = 231 (M+, 3), 57 (100).
Anal. Calcd for C11H21NO2S: C, 57.11; H, 9.15; N, 6.05. Found: C,
57.06; H, 8.94; N, 5.94.
IR (neat): 1627, 1297, 1117 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.06 (d, J = 6.3 Hz, 3 H), 1.49 (s,
9 H), 1.57–1.85 (m, 4 H), 2.03–2.15 (m, 2 H), 2.29–2.39 (m, 1 H),
2.45–2.53 (m, 1 H), 3.50–3.57 (m, 1 H).
N-Cyclooctylidine-tert-butanesulfonamide (4d)
Mp 153–154 °C; Rf = 0.56 (PE–EtOAc, 10:1).
IR (neat): 1614, 1296, 1122 cm–1.
13C NMR (75 MHz, CDCl3): d = 16.3, 23.8, 24.9, 27.9, 36.3, 37.1,
43.9, 58.8, 195.6.
1H NMR (200 MHz, CDCl3): d = 1.46 (s, 9 H), 1.51–1.56 (m, 5 H),
1.80–1.98 (m, 5 H), 2.52 (t, J = 6.2 Hz, 2 H), 2.96 (t, J = 6.2 Hz, 2
H).
EI-MS: m/z (%) = 231 (M+, 4), 57 (100).
Anal. Calcd for C11H21NO2S: C, 57.11; H, 9.15; N, 6.05. Found: C,
56.93; H, 8.95; N, 5.94.
13C NMR (50 MHz, CDCl3): d = 23.7, 23.9, 24.6, 26.1, 27.6, 29.0,
36.9, 39.4, 58.5, 199.2.
N-2-Phenylcyclohexylidine-tert-butanesulfonamide (4g)
Mp 133–134 °C; Rf = 0.70 (PE–EtOAc, 10:1).
EI-MS: m/z (%) = 245 (M+, 4), 57 (100).
Anal. Calcd for C12H23NO2S: C, 58.74; H, 9.45; N, 5.71. Found: C,
58.51; H, 9.36; N, 5.56.
IR (neat): 1627, 1284, 1120 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.18 (s, 9 H), 1.50–2.33 (m, 6 H),
2.48–2.63 (m, 1 H), 3.52–3.68 (m, 2 H), 7.11–7.35 (m, 5 H).
N-2-Methylcyclopentylidine-tert-butanesulfonamide (4e)
Mp 158–159 °C; Rf = 0.41 (PE–EtOAc, 10:1).
13C NMR (50 MHz, CDCl3) d = 23.47, 25.10, 27.69, 34.59, 36.43,
55.24, 58.83, 126.80, 127.94, 128.63, 139.32, 193.35.
IR (neat): 1640, 1300, 1121 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.18 (d, J = 6.8 Hz, 3 H), 1.48 (s,
9 H), 1.57–1.87 (m, 2 H), 1.93–2.16 (m, 2 H), 2.68–2.88 (m, 2 H),
2.99–3.13 (m, 1 H).
EI-MS: m/z (%) = 293 (M+, 8), 57 (100).
Anal. Calcd for C16H23NO2S: C, 65.49; H, 7.90; N, 4.77. Found: C,
65.63; H, 7.95; N, 4.72.
13C NMR (50 MHz, CDCl3): d = 15.5, 22.8, 23.8, 32.0, 34.4, 45.1,
58.4, 202.2.
Synthesis 2006, No. 10, 1705–1710 © Thieme Stuttgart · New York

1708
S. Chen et al.
SPECIAL TOPIC
Reaction of EDA with Ketimines; General Procedure
1H NMR (200 MHz, CDCl3): d = 1.27 (t, J = 7.2 Hz, 3 H), 1.39 (s,
9 H), 1.46–1.59 (m, 10 H), 2.08–2.22 (m, 4 H), 4.22 (q, J = 7.2 Hz,
2 H), 4.24 (br s, 1 H).
A dry 50-mL flask equipped with a 10-mL dropping funnel was
charged with anhyd THF (8 mL) under N2. i-Pr2NH (1.4 mmol) and
n-BuLi (2.0 M, hexane; 1.3 mmol) were added sequentially via sy-
ringe at –78 °C (dry ice–acetone). A solution of EDA (1.3 mmol) in
anhyd THF (5 mL) was added dropwise over 5 min at the same tem-
perature. After the resulting solution was stirred for 5 min, HMPA
(6.5 mmol) was introduced, and the solution was stirred for another
5 min. Then a solution of N-tert-butanesulfonylimine (1 mmol) in
anhyd THF (8 mL) was added dropwise over 30 min via the drop-
ping funnel at –78 °C. The reaction was continued for 4–24 h at the
same temperature until the imine was no longer present (TLC). The
reaction was quenched with a sat. aq solution of NH4Cl (3 mL) at
–78 °C. The resulting mixture was extracted with CH2Cl2 (3 × 15
mL) and the combined organic layers were dried over anhyd
Na2SO4. The solvent was removed under reduced pressure to give
the crude product, which was purified by column chromatography.
13C NMR (50 MHz, CDCl3): d = 14.4, 21.9, 23.9, 24.8, 27.9, 31.7,
60.1, 60.5, 62.34, 166.0.
EI-MS: m/z (%) = 359 (M+, 8), 29 (100).
HRMS: m/z calcd for C16H29N3O4S: 359.1879; found: 359.1879.
Ethyl 2-Diazo-2-{[1¢-(tert-butylsulfonyl)amino]-2¢-methylcyclo-
pentyl}acetate (5e)
Mp 102–103 °C; Rf = 0.43 (PE–EtOAc, 5:1).
IR (neat): 3291, 2094, 1684, 1315, 1127 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.05 (d, J = 6.8 Hz, 3 H), 1.28 (t,
J = 7.2 Hz, 3 H), 1.40 (s, 9 H), 1.64–2.12 (m, 5 H), 2.26–2.36 (m, 1
H), 2.56–2.64 (m, 1 H), 4.24 (q, J = 7.2 Hz, 2 H), 4.89 (br s, 1 H).
13C NMR (50 MHz, CDCl3): d = 14.4, 16.9, 20.3, 24.1, 30.3, 32.3,
43.1, 59.9, 60.8, 65.4, 166.5.
Ethyl 2-Diazo-2-{[1¢-(tert-butylsulfonyl)amino]cyclopentyl}ace-
tate (5a)
Mp 80–81 °C; Rf = 0.39 (PE–EtOAc, 5:1).
EI-MS: m/z (%) = 331 (M+, 6), 303 [(M – 28)+, 2], 57 (100).
IR (neat): 3282, 2099, 1681, 1318, 1302, 1125 cm–1.
Anal. Calcd for C14H25N3O4S: C, 50.73; H, 7.60; N, 12.68. Found:
C, 50.98; H, 7.70; N, 12.55.
1H NMR (300 MHz, CDCl3): d = 1.28 (t, J = 7.2 Hz, 3 H), 1.39 (s,
9 H), 1.65–1.75 (m, 2 H), 1.77–1.87 (m, 2 H), 2.05–2.19 (m, 4 H),
4.25 (q, J = 7.2 Hz, 2 H), 4.69 (br s, 1 H).
Ethyl 2-Diazo-2-{[1¢-(tert-butylsulfonyl)amino]-2¢-methylcyclo-
hexyl}acetate (5f)
Mp 111–112 °C; Rf = 0.65 (PE–EtOAc, 5:1).
13C NMR (75 MHz, CDCl3): d = 14.37, 22.31, 23.88, 24.18, 38.11,
59.62, 60.62, 64.14, 166.23.
IR (neat): 3291, 2094, 1684, 1315, 1127 cm–1.
EI-MS: m/z (%) = 317 (M+, 7), 289 [(M – 28)+, 18], 57 (100).
1H NMR (200 MHz, CDCl3): d = 1.17 (d, J = 7.6 Hz, 3 H), 1.28 (t,
J = 7.2 Hz, 3 H), 1.38 (s, 9 H), 1.46–1.78 (m, 7 H), 2.45–2.52 (m, 1
H), 2.77–2.79 (m, 1 H), 4.22 (q, J = 7.2 Hz, 2 H), 4.34 (br s, 1 H).
13C NMR (75 MHz, CDCl3): d = 13.7, 14.3, 18.3, 22.4, 23.9, 27.8,
28.9, 34.2, 60.0, 60.4, 61.8, 166.1.
Anal. Calcd for C13H23N3O4S: C, 49.19; H, 7.30; N, 13.24. Found:
C, 49.28; H, 7.29; N, 13.39.
Ethyl 2-Diazo-2-{[1¢-(tert-butylsulfonyl)amino]cyclohexyl}ace-
tate (5b)
Mp 83–84 °C; Rf = 0.39 (PE–EtOAc, 5:1).
EI-MS: m/z (%) = 345 (M+, 5), 317 [(M – 28)+, 3], 57 (100).
Anal. Calcd for C15H27N3O4S: C, 52.15; H, 7.88; N, 12.16. Found:
C, 52.30; H, 7.85; N, 11.93.
IR (neat): 3275, 2101, 1683, 1313, 1273, 1125 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.28 (t, J = 7.2 Hz, 3 H), 1.33–1.35
(m, 2 H), 1.39 (s, 9 H), 1.61–1.75 (m, 6 H), 2.42–2.46 (m, 2 H), 4.23
(q, J = 7.2 Hz, 2 H), 4.37 (br s, 1 H).
Ethyl 2-Diazo-2-{[1¢-(tert-butylsulfonyl)amino]-2¢-phenylcyclo-
hexyl}acetate (5g)
Oil; Rf = 0.27 (PE–EtOAc, 5:1).
13C NMR (75 MHz, CDCl3): d = 14.4, 22.3, 23.9, 25.1, 35.6, 58.5,
59.8, 60.5, 165.9.
IR (neat): 2098, 1686, 1289, 1129 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.22 (t, J = 7.2 Hz, 3 H), 1.30 (s,
9 H), 1.41–1.69 (m, 2 H), 1.85–1.87 (m, 2 H), 1.98–2.07 (m, 2 H),
2.20–2.27 (m, 1 H), 2.58–2.65 (m, 1 H), 3.44–3.45 (m, 1 H), 4.12
(q, J = 7.2 Hz, 2 H), 4.59 (br s, 1 H), 7.28–7.34 (m, 5 H).
EI-MS: m/z (%) = 331 (M+, 7), 303 [(M – 28)+, 16], 29 (100).
Anal. Calcd for C14H25N3O4S: C, 50.73; H, 7.60; N, 12.68. Found:
C, 50.86; H, 7.71; N, 12.53.
13C NMR (75 MHz, CDCl3): d = 14.4, 21.8, 23.1, 24.1, 28.3, 31.5,
50.9, 59.8, 60.3, 60.5, 127.4, 128.5, 129.2, 140.9, 166.2.
Ethyl 2-Diazo-2-{[1¢-(tert-butylsulfonyl)amino]cycloheptyl}ace-
tate (5c)
Mp 114–115 °C; Rf = 0.29 (PE–EtOAc, 5:1).
EI-MS: m/z (%) = 407 (M+, 2), 57 (100).
IR (neat): 3284, 2097, 1684, 1315, 1127 cm–1.
HRMS: m/z calcd for C20H29N3O4S: 407.1879; found: 407.1879.
1H NMR (300 MHz, CDCl3): d = 1.28 (t, J = 7.2 Hz, 3 H), 1.39 (s,
9 H), 1.54–1.61 (m, 8 H), 2.02–2.11 (m, 2 H), 2.23–2.31 (m, 2 H),
4.24 (q, J = 7.2 Hz, 2 H), 4.42 (br s, 1 H).
Rh2(OAc)4-Catalyzed Reaction of Diazo Compounds 4a–g;
General Procedure
In a three-necked round-bottom flask equipped with a dropping fun-
nel and a condenser, Rh2(OAc)4 was dissolved in anhyd CH2Cl2 or
DCE (5 mL) under N2. This mixture was heated to reflux, a solution
of diazo substrate in anhyd CH2Cl2 or DCE (5 mL) was added drop-
wise, and the resulting solution was heated under reflux until the re-
action was complete (IR and TLC). The solvent was removed under
reduced pressure and the crude residue was purified by column
chromatography.
13C NMR (75 MHz, CDCl3): d = 14.34, 21.79, 23.93, 29.21, 37.75,
59.89, 60.54, 61.96, 166.15.
EI-MS: m/z (%) = 317 [(M – 28)+, 4], 57 (100).
Anal. Calcd for C15H27N3O4S: C, 52.15; H, 7.88; N, 12.16. Found:
C, 52.38; H, 7.79; N, 12.01.
Ethyl 2-Diazo-2-{[1¢-(tert-butylsulfonyl)amino]cyclooctyl}ace-
tate (5d)
Mp 128–129 °C; Rf = 0.23 (PE–EtOAc, 5:1).
1-[(tert-Butylsulfonyl)amino]-2-carboethoxycyclohexene (6a)
Mp 65–66 °C; Rf = 0.62 (PE–EtOAc, 10:1).
IR (neat): 3288, 2097, 1686, 1319, 1125 cm–1.
Synthesis 2006, No. 10, 1705–1710 © Thieme Stuttgart · New York

SPECIAL TOPIC
Cyclic N-tert-Butylsulfonyl Enamines
1709
IR (neat): 1659, 1606, 1235, 1132 cm–1.
N-2-Carboethoxyl-7-methylcycloheptylidine-tert-butane-
sulfonamide (7f)
Mp 165–166 °C; Rf = 0.32 (PE–EtOAc, 10:1).
1H NMR (200 MHz, CDCl3): d = 1.30 (t, J = 7.2 Hz, 3 H), 1.44 (s,
9 H), 1.53–1.65 (m, 4 H), 2.30–2.35 (m, 2 H), 2.68–2.73 (m, 2 H),
4.20 (q, J = 7.2 Hz, 2 H), 11.24 (br s, 1 H).
IR (neat): 1736, 1621, 1304, 1122 cm–1.
13C NMR (50 MHz, CDCl3): d = 14.1, 21.7, 21.7, 24.2, 27.1, 60.5,
61.2, 104.1, 151.9, 170.1.
1H NMR (300 MHz, CDCl3): d = 1.25 (t, J = 7.2 Hz, 3 H), 1.33 (d,
J = 6.9 Hz, 3 H), 1.45 (s, 9 H), 1.64–1.72 (m, 2 H), 1.76–1.91 (m, 3
H), 2.04–2.09 (m, 1 H), 2.18 (dd, J = 11.4 Hz, 5.1 Hz, 1 H), 2.73
(dd, J = 8.4, 8.1 Hz, 1 H), 3.18–3.28 (m, 1 H), 3.88–3.89 (m, 1 H),
4.13 (q, J = 7.2 Hz, 2 H).
EI-MS: m/z (%) = 289 (M+, 14), 57 (100).
Anal. Calcd for C13H23NO4S: C, 53.95; H, 8.01; N, 4.84. Found: C,
53.79; H, 7.96; N, 4.62.
13C NMR (75 MHz, CDCl3): d = 14.1, 17.2, 19.8, 23.7, 33.3, 34.8,
36.0, 38.5, 40.4, 58.9, 60.4, 171.9, 197.2.
1-[(tert-Butylsulfonyl)amino]-2-carboethoxycycloheptene (6b)
Oil; Rf = 0.31 (PE–EtOAc, 10:1).
EI-MS: m/z (%) = 317 (M+, 3), 57 (100).
IR (neat): 3264, 1721, 1306, 1220, 1128 cm–1.
Anal. Calcd for C15H27NO4S: C, 56.75; H, 8.57; N, 4.41. Found: C,
56.94; H, 8.33; N, 4.37.
1H NMR (300 MHz, CDCl3): d = 1.34 (t, J = 7.2 Hz, 3 H), 1.42 (s,
9 H), 1.62–1.67 (m, 6 H), 2.53 (t, J = 6.0 Hz, 2 H), 2.67 (t, J = 6.0
Hz, 2 H), 4.27 (q, J = 7.2 Hz, 2 H), 5.77 (br s, 1 H).
1-[(tert-Butylsulfonyl)amino]-2-carboethoxy-7-phenylcyclo-
heptene (6g)
Oil; Rf = 0.57 (PE–EtOAc, 10:1).
13C NMR (75 MHz, CDCl3): d = 14.1, 24.2, 25.9, 27.5, 27.7, 30.9,
32.2, 60.9, 61.1, 118.9, 154.7, 165.8.
IR (neat): 1655, 1597, 1231, 1133 cm–1.
EI-MS: m/z (%) = 303 (M+, 9), 57 (100).
1H NMR (300 MHz, CDCl3): d = 1.33 (t, J = 7.2 Hz, 3 H), 140 (s, 9
H), 1.56–1.72 (m, 4 H), 1.85–1.95 (m, 1 H), 2.01–2.12 (m, 1 H),
2.25–2.31 (m, 1 H), 2.68–2.75 (m, 1 H), 4.26 (q, J = 7.2 Hz, 2 H),
4.95 (t, J = 5.4 Hz, 1 H), 6.97–7.35 (m, 5 H), 11.48 (s, 1 H).
Anal. Calcd for C14H25NO4S: C, 55.42; H, 8.30; N, 4.62. Found: C,
55.13; H, 8.18; N, 4.47.
1-[(tert-Butylsulfonyl)amino]-2-carboethoxycyclooctene (6c)
Oil; Rf = 0.57 (PE–EtOAc, 10:1).
13C NMR (75 MHz, CDCl3): d = 14.2, 24.3, 24.4, 24.7, 25.6, 29.4,
43.50, 60.9, 61.1, 112.2, 126.0, 126.9, 128.6, 139.1, 156.7, 170.9.
IR (neat): 1654, 1600, 1236, 1135 cm–1.
EI-MS: m/z (%) = 379 (M+, 7), 57 (100).
1H NMR (300 MHz, CDCl3): d = 1.30 (t, J = 7.2 Hz, 3 H), 1.43 (s,
9 H), 1.47–1.60 (m, 6 H), 1.80–1.82 (m, 2 H), 2.47 (t, J = 6.1 Hz, 2
H), 2.85 (t, J = 6.1 Hz, 2 H), 4.21 (q, J = 7.2 Hz, 2 H), 11.42 (br s,
1 H). 13C NMR (75 MHz, CDCl3): d = 14.2, 24.3, 25.6, 26.2, 26.8,
27.2, 29.7, 30.3, 60.6, 61.2, 106.9, 155.2, 170.0.
HRMS: m/z calcd for C20H29NO4S: 379.1817; found: 379.1820.
N-2-Carboethoxyl-7-phenylcycloheptylidine-tert-butane-
sulfonamide (8)
Mp 115–116 °C; Rf = 0.31 (PE–EtOAc, 10:1).
EI-MS: m/z (%) = 317 (M+, 8), 57 (100).
IR (neat): 1734, 1625, 1301, 1122 cm–1.
Anal. Calcd for C15H27NO4S: C, 56.75; H, 8.57; N, 4.41. Found: C,
56.54; H, 8.70; N, 4.30.
1H NMR (300 MHz, CDCl3): d = 1.27 (t, J = 7.2 Hz, 3 H), 1.51 (s,
9 H), 1.57–1.72 (m, 2 H), 1.81–2.22 (m, 4 H), 2.68–2.78 (m, 2 H),
3.05–3.16 (m, 1 H), 4.11 (q, J = 7.2 Hz, 2 H), 5.17 (br s, 1 H), 7.17–
7.41 (m, 5 H).
1-[(tert-Butylsulfonyl)amino]-2-carboethoxycyclononene (6d)
Mp 86–87 °C; Rf = 0.26 (PE–EtOAc, 10:1).
13C NMR (75 MHz, CDCl3): d = 14.1, 20.4, 23.8, 30.5, 36.3, 36.4,
41.8, 47.9, 59.2, 60.4, 126.8, 127.5, 128.8, 137.2, 171.6, 194.7.
IR (neat): 3254, 1720, 1307, 1128 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.33 (t, J = 7.2 Hz, 3 H), 1.43 (s,
9 H), 1.44–1.51 (m, 5 H), 1.72–1.83 (m, 5 H), 2.62–2.66 (m, 4 H),
4.27 (q, J = 7.2 Hz, 2 H), 5.57 (br s, 1 H).
EI-MS: m/z (%) = 379 (M+, 10), 259 (100).
Anal. Calcd for C20H29NO4S: C, 63.30; H, 7.70; N, 3.69. Found: C,
63.36; H, 7.65; N, 3.69.
13C NMR (75 MHz, CDCl3): d = 14.1, 22.9, 24.2, 25.5, 25.7, 28.0,
29.3, 30.3, 33.6, 60.8, 61.1, 120.9, 158.8, 165.6.
EI-MS: m/z (%) = 331 (M+, 2), 57 (100).
Acknowledgment
Anal. Calcd for C16H29NO4S: C, 57.98; H, 8.82; N, 4.23. Found: C,
57.79; H, 8.74; N, 4.14.
The project was generously supported by Natural Science Founda-
tion of China (Grant Nos. 20572002, 20521202, 20225205, and
20390050) and the Ministry of Education of China.
1-[(tert-Butylsulfonyl)amino]-2-carboethoxy-3-methylcyclo-
hexene (6e)
Mp 91–92 °C; Rf = 0.63 (PE–EtOAc, 10:1).
References
IR (neat): 1687, 1600, 1301, 1131 cm–1.
(1) For comprehensive reviews on a-diazocarbonyl compounds,
see: (a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern
Catalytic Methods for Organic Synthesis with Diazo
Compounds; Wiley-Interscience: New York, 1998. (b) Ye,
T.; McKervey, M. A. Chem. Rev. 1994, 44, 1091.
(2) (a) Ye, T.; McKervey, M. A. Tetrahedron 1992, 48, 8007.
(b) Baudouy, R.; Gore, J.; Ruest, L. Tetrahedron 1987, 43,
1099. (c) Damour, D.; Renaudon, A.; Mignani, S. Synlett
1995, 111. (d) Nagao, K.; Chiba, M.; Kim, S.-W. Synthesis
1983, 197.
1H NMR (300 MHz, CDCl3): d = 1.08 (d, J = 6.6 Hz, 3 H), 1.31 (t,
J = 6.9 Hz, 3 H), 1.43 (s, 9 H), 1.62–1.67 (m, 4 H), 2.44–2.61 (m, 1
H), 2.82–2.89 (m, 2 H), 4.21 (q, J = 6.9 Hz, 2 H), 11.29 (br s, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.1, 16.9, 21.2, 24.2, 27.2, 27.6,
29.0, 60.5, 61.3, 109.5, 151.9, 170.0.
EI-MS: m/z (%) = 303 (M+, 7), 168 (100).
Anal. Calcd for C14H25NO4S: C, 55.42; H, 8.30; N, 4.62. Found: C,
55.17; H, 8.16; N, 4.45.
Synthesis 2006, No. 10, 1705–1710 © Thieme Stuttgart · New York

1710
S. Chen et al.
SPECIAL TOPIC
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(4) Very recently Aggarwal and co-workers reported a rare case
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Synthesis 2006, No. 10, 1705–1710 © Thieme Stuttgart · New York